Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus
Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus
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DOI：
10.4049/jimmunol.172.12.7821
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Tsokos, GC
中科院分区：
文献类型：
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作者：
Krishnan, S;Nambiar, MP;Tsokos, GC
系统性红斑狼疮（SLE）患者的T淋巴细胞对适当刺激的反应表现出细胞内酪氨酸磷酸化和游离钙反应的增加和加快。我们已经探讨了脂筏的组成和动力学是否是负责异常的T细胞反应在SLE。SLE T细胞产生并拥有更高量的含有神经节苷脂的脂筏，并且与正常T细胞不同，SLE T细胞脂筏包括FcR γ和活化的Syk激酶。IgM抗CD3 Ab介导的TCR复合物加帽在SLE T细胞中发生得更快，并伴随着肌动蛋白聚合动力学的显著加速。这些发现的意义是显而易见的，从观察到的脂筏交联引起SLE T细胞更早和更高的钙反应。因此，我们认为脂筏信号机制的改变是SLE T细胞反应增强和加速的重要机制。
In response to appropriate stimulation, T lymphocytes from systemic lupus erythematosus (SLE) patients exhibit increased and faster intracellular tyrosine phosphorylation and free calcium responses. We have explored whether the composition and dynamics of lipid rafts are responsible for the abnormal T cell responses in SLE. SLE T cells generate and possess higher amounts of ganglioside-containing lipid rafts and, unlike normal T cells, SLE T cell lipid rafts include FcRgamma and activated Syk kinase. IgM anti-CD3 Ab-mediated capping of TCR complexes occurs more rapidly in SLE T cells and concomitant with dramatic acceleration of actin polymerization kinetics. The significance of these findings is evident from the observation that cross-linking of lipid rafts evokes earlier and higher calcium responses in SLE T cells. Thus, we propose that alterations in the lipid raft signaling machinery represent an important mechanism that is responsible for the heightened and accelerated T cell responses in SLE.